Mice, homozygous for disrupted ganglioside GM2/GD2 synthase (EC 2.4.1.94) gene and lacking all complex gangliosides, do not display any major neurologic abnormalities. Further examination of these mutant mice, however, revealed that the males were sterile and aspermatogenic. In the seminiferous tubules of the mutant mice, a number of multinuclear giant cells and vacuolated Sertoli cells were observed. The levels of testosterone in the serum of these mice were very low, although testosterone production equaled that produced in wild-type mice. Testosterone was found to be accumulated in interstitial Leydig cells, and intratesticularly injected testosterone was poorly drained in seminiferous f luid in the mutant mice. These results suggested that complex gangliosides are essential in the transport of testosterone to the seminiferous tubules and bloodstream from Leydig cells. Our results provide insights into roles of gangliosides in vivo.

No abstract

A beta-variant hemoglobin, first misjudged as a marked elevation of Hb A1, was found in a 68-year-old Japanese female with diabetes mellitus. This hemoglobin was isolated by Bio-Rex 70 chromatography combined with chromatofocusing, and was found to be Hb Hope, beta 136(H14)Gly----Asp, by classical and high performance liquid chromatographic peptide mapping techniques. Intrinsic oxygen affinity of this hemoglobin was approximately one-third as compared with that of Hb A0. This property was still observed in the constituent beta subunits isolated. Effects of such allosteric effectors as H+ (at a fixed concentration of Cl-), anion (Cl-), 2,3-diphosphoglycerate and carbon dioxide were more or less depressed. Among others, a marked reduction in the carbamate effect should be noted in a structural interpretation of the functional modifications. Subunit cooperativity, on the contrary, was not different from that in Hb A0 (n = 2.8-2.9). Explanation of these altered functions were attempted on the basis of the altered structure. The reduced stability of Hb Hope is also described.

No abstract

High leptin levels in Prader-Willi (P-W) syndrome may occur as a result of the existence of leptin resistance, because a hypothalamic disturbance may underlay this disorder. In order to study whether there is a defective action of leptin on the hypothalamus in P-W syndrome, we have measured leptin and insulin twice during the daily profile of blood glucose, comparing the results with the recent reports. The patient was a 22-year-old female, who showed the typical feature of P-W syndrome complicated overt diabetes. This case of P-W syndrome was only made to maintain a diet of 1840 kcal/day of examination under hospitalization and was not made to maintain a calorie diet on any other day of examination in clinic. There was no reduction of leptin observed during the day, especially around noon and mid-afternoon, both under hospitalization and in clinic. Our experience suggests that an absence of the normal fall in leptin during the day was not related to eating pattern in this case, but to the defective action of leptin on the hypothalamus as well as excessive production by adipose tissue.